The objective is to identify and characterize the humoral agent or system that causes the elevation of blood pressure in chronic one-kidney hypertension. The blood pressure of rabbits with this form of hypertension was lowered to normal by direct immunization with renin-free preparations from hog kidney cortex. It was concluded that an unknown substance in the hog kidney preparations elicited an antibody in the hypertensive rabbits that cross-reacted with a factor that is essential for the maintainance of an elevated blood pressure level. A search for such a factor in rabbit kidney cortex has disclosed a new hypertensive substance, renopressin, which is totally unlike renin. Subcutaneous injection of renopressin into normal rabbits causes, after 48 hours or more, a slow, moderate increase in blood pressure that is sustained indefinitely without further injections. The blood pressures of both one-kidney and renopressin hypertensive rabbits can be lowered to normal with an antibody elicited by an antigen in renin-free hog kidney extracts. The antibody reacts with the mediator of both forms of hypertension. Thus the mediator is presumably identical in both forms and is similar or identical to the antigen. Renopressin produces hypertension and may be the mediator. However, its action persists indefinitely after injections have stopped. It is unlikely that it would survive for so long a time within the organism. Instead, it may trigger the synthesis and release of a second substance that is the mediator. We plan to isolate and characterize the postulated mediator (antigen) as well as renopressin so that we may understand how they may cause chronic hypertension in rabbits and possibly hypertension in human beings.